Research in the Kim laboratory is supported by the Celgene Corporation, Doris Duke Charitable Foundation, LEO Pharma, and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (K08AR065577, R01AR070116, R01AR077007, and R21AI167047) (to B.S.K.). A.M.T. and M.R.M. are supported by National Institute of Allergy and Infectious Diseases (NIAID) (T32AI007163). A.M.T. and L.K.O. are supported by National Heart, Lung, and Blood Institute (NHLBI) (T32HL007317). A.M.T. is supported by NIAID (F30AI154912). Research in the Gereau laboratory involving human dorsal root ganglia research is supported by National Institute of Neurological Disorders and Strokes (NINDS) (R01NS042595) (to R.W.G.). Research in the Alexander-Brett laboratory is supported by NHLBI (R01HL152245) and the Burroughs Welcome Fund (1014685) (to J.A.B). Research in the Cavalli laboratory is supported by the McDonnell Center for Cellular and Molecular Neurobiology and NINDS (R01NS111719) (to V.C.). O.A. is supported by the postdoctoral fellowship from the McDonnell Center for Cellular and Molecular Neurobiology. Research in the Davidson laboratory is supported by NINDS (RF1NS113881) (to S.D.). Research in the Hu laboratory is supported by National Institute for Alcohol Abuse and Alcoholism (NIAAA) (R01AA027065), NIAMS (R01AR077183), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01DK103901) (to H.H.

Background: Chronic pruritus of unknown origin (CPUO) is a highly debilitating disease that lacks effective treatments. This study explores a new therapeutic strategy with dupilumab. Objectives: To examine whether patients with CPUO demonstrate clinical response to dupilumab. Patients and methods: This is a retrospective case series examining all patients with CPUO who were treated with dupilumab from March 2017 to December 2019 at a tertiary referral clinic at Washington University School of Medicine in St. Louis, MO. Numerical rating scale (NRS) itch score changes over time were recorded and analyzed. Results: Fifteen patients (67% women; mean [SD] age, 68.7 [12.6] years [range, 42-88 years]) were included in the analysis. All patients had a diagnosis of CPUO for a mean [SD] 2.6 [2.8] years. The median [IQR] pruritus NRS itch score before dupilumab injection was 8 [8-10] and the final median [IQR] NRS itch score was 1 [0-2.5]. The mean [SD] reduction in the NRS itch score was 7.0 [1.9]. Dupilumab was well tolerated with one report of mild injection site reaction that was self-resolving. Conclusion:This study suggests that dupilumab may be an effective treatment for patients with CPUO and supports the design of future randomized placebo-controlled trials to prove its efficacy.